Glossary

acquired immune response: Immunity mediated by lymphocytes and characterized by antigen-specificity and memory.

acute phase proteins: Serum proteins, mostly produced in the liver, which rapidly change in concentration (some increase, some decrease) during the initiation of an inflammatory response.

addressin: Cell adhesion molecule present on the luminal surface of blood and lymph vessel endothelium, and recognized by homing molecules which direct leukocytes to tissues with the appropriate 'address'.

adjuvant: Any substance which nonspecifically enhances the immune response to antigen.

affinity (intrinsic affinity): The strength of binding (affinity constant) between a receptor (e.g. one antigen-binding site on an antibody) and a ligand (e.g. epitope on an antigen).

affinity chromatography: The use of immobilized antibody (or antigen) to select specific antigen (or antibody) from a mixture. The purified ligand is then released by disrupting for antibody–antigen interaction, for example by changing the pH.

allele: Variants of a polymorphic gene at a given genetic locus.

allelic exclusion: The phenomenon whereby, following successful rearrangement of one allele of an antigen receptor gene, rearrangement of the other parental allele is suppressed.

anaphylaxis: An often fatal hypersensitivity reaction, triggered by IgE or anaphylatoxin-mediated mast cell degranulation, leading to anaphylactic shock due to vasodilatation and smooth muscle contraction.

antigen: Any molecule capable of being recognized by an antibody or T-cell receptor.

antigen-presenting cell (APC): A term most commonly used when referring to cells that present processed antigenic peptide and MHC class II molecules to the T-cell receptor on CD4 + T-cells, e.g. dendritic cells, macrophages, B-cells. Note, however, that most types of cell are able to present antigenic peptides with MHC class I to CD8 + T-cells, e.g. as occurs with virally infected cells.

antigenic determinant: A cluster of epitopes (see epitope).

apoptosis: A form of programmed cell death, characterized by endonuclease digestion of DNA.

avidity (functional affinity): The binding strength between two molecules (e.g. antibody and antigen) taking into account the valency of the interaction. Thus the avidity will always be equal to or greater than the intrinsic affinity (see affinity).

β2-microglobulin: A 12 kDa protein, not itself encoded within the MHC, but forming part of the structure of MHC class I-encoded molecules.

B-1/B-2 cells: The two major subpopulations of B lymphocytes. B-1 cells bear high levels of surface IgM, lower levels of surface IgD, are CD43 + , CD23 - and most express the cell surface antigen CD5; they are self-renewing, and frequently secrete high levels of antibody which binds to a range of antigens (‘polyspecificity’) with a relatively low affinity. The majority of B cells, however, are B-2 which express low levels of surface IgM, higher levels of surface IgD, do not express CD5, and are CD43 - , CD23 + ; they are directly generated from precursors in the bone marrow, and secrete highly specific antibody.

basophil: A type of granulocyte found in the blood and resembling the tissue mast cell.

BCG (bacille Calmette–Guérin): Attenuated Mycobacterium tuberculosis used both as a specific vaccine for tuberculosis and as an adjuvant.

biolistics: The use of small particles, e.g. colloidal gold, as a vehicle for carrying agents (drugs, nucleic acid, etc.) into a cell. Following coating with the desired agent(s), the particles are fired into the dermis of the recipient using a helium-powered gun.

bispecific antibody: An artificially produced hybrid antibody in which each of the two antigen-binding arms is specific for a different antigenic epitope. Such antibodies, which can be produced either by chemical cross-linkage or by recombinant DNA techniques, can be used to link together two different antigens or cells, e.g. a cytotoxic T-cell and a tumor cell.

bursa of Fabricius: A primary lymphoid organ in avian species, located at the cloacal-hind gut junction; it is the site of B-cell maturation.

central memory: Immunological memory that is dependent on CCR7+ T-cells which, under the influence of chemokines, travel to secondary lymphoid organs where they give rise to CCR7– effector memory T-cells.

central tolerance: Specific immunological tolerance due to the induction of lymphocyte apoptosis or anergy within the primary lymphoid organs (bone marrow in the case of B-cell tolerance and the thymus for T-cells).

chemokines: A family of structurally-related cytokines which selectively induce chemotaxis and activation of leukocytes. They also play important roles in lymphoid organ development, cell compartmentalization within lymphoid tissues, Th1/Th2 development, angiogenesis and wound healing.

chemotaxis: Movement of cells up a concentration gradient of chemotactic factors.

combinatorial diversity: That component of antibody and T-cell receptor (TCR) diversity that is generated by the recombination of variable (V), diversity (D, for immunoglobulin heavy chains, and for TCR β and δ chains) and joining (J) gene segments.

complement: A group of serum proteins, some of which act in an enzymatic cascade, producing effector molecules involved in inflammation (C3a, C5a), phagocytosis (C3b), and cell lysis (C5b–9).

C-reactive protein: An acute phase protein which is able to bind to the surface of microorganisms where it functions as a stimulator of the classical pathway of complement activation, and as an opsonin for phagocytosis.

dendritic cell: Refers to an interdigitating dendritic cell which is MHC class II-positive, Fc receptor-negative, and presents processed antigens to T-cells in the T-cell areas of secondary lymphoid tissues. (NB a different cell type to follicular dendritic cells).

differential splicing: The utilization and splicing of different exons from a primary RNA transcript in order to generate different mRNA sequences.

differentiation antigen: A cell surface molecule expressed at a particular stage of development or on cells of a given lineage.

DiGeorge syndrome: Immunodeficiency caused by a congenital failure in thymic development resulting in a lack of mature functional T-cells.

diversity (D) gene segments: Found in the immunoglobulin heavy chain gene and T-cell receptor β and δ gene loci between the Vand Jgene segments. Encode part of the third hypervariable region in these antigen receptor chains.

ELISA (enzyme-linked immunosorbent assay): Assay for detection or quantitation of an antibody or antigen using a ligand (e.g. an anti-immunoglobulin) conjugated to an enzyme which changes the color of a substrate.

endocytosis: Cellular ingestion of macromolecules by invagination of plasma membrane to produce an intracellular vesicle which encloses the ingested material.

endogenous: From within.

endosomes: Intracellular smooth surfaced vesicles in which endocytosed material passes on its way to the lysosomes.

Fab: Monovalent antigen-binding fragment obtained following papain digestion of immunoglobulin. Consists of an intact light chain and the N-terminal V H and C H1 domains of the heavy chain.

F(ab´)2: Bivalent antigen-binding fragment obtained following pepsin digestion of immunoglobulin. Consists of both light chains and the N-terminal part of both heavy chains linked by disulfide bonds.

Fas: A member of the TNF receptor gene family. Engagement of Fas (CD95) on the surface of the cell by the Fas ligand (CD178) present on cytotoxic cells, can trigger apoptosis in the Fas-bearing target cell.

Fc: Crystallizable, non-antigen-binding fragment of an immunoglobulin molecule obtained following papain digestion. Consists of the C-terminal portion of both heavy chains which is responsible for binding to Fc receptors and C1q.

fibroblast: Connective tissue cell which produces collagen and plays an important part in wound healing.

fluorescein isothiocyanate (FITC): Green fluorescent dye used to ‘tag’ antibodies for use in immunofluorescence.

fluorescent antibody: An antibody conjugated to a fluorescent dye such as FITC.

foam cell: Macrophages which have engulfed low density lipoproteins. They are characteristically present in atherosclerotic plaques.

follicular dendritic cell: MHC class II-negative Fc receptor-positive dendritic cells which bear immune complexes on their surface and are involved in the generation of antibody-secreting cells and maintenance of B-cell memory in germinal centres. (N.B. a different cell type to interdigitating dendritic cells).

foxp3: A transcription factor present in the nucleus of most regulatory T-cells.

framework regions: The relatively conserved amino acid sequences which flank the hypervariable regions in immunoglobulin and T-cell receptor variable regions and maintain a common overall structure for all V-region domains.

granuloma: A tissue nodule containing proliferating lymphocytes, fibroblasts, and giant cells and epithelioid cells (both derived from activated macrophages), which forms due to inflammation in response to chronic infection or persistence of antigen in the tissues.

granzymes: Serine esterases present in the granules of cytotoxic T lymphocytes and NK cells. They induce apoptosis in the target cell which they enter through perforin channels inserted into the target cell membrane by the cytotoxic lymphocyte.

haplotype: The set of allelic variants present at a given genetic region.

hapten: A low molecular weight molecule that is recognized by preformed antibody but is not itself immunogenic unless conjugated to a ‘carrier’ molecule which provides epitopes recognized by helper T-cells.

helper T lymphocyte (Th): A subclass of T-cells which provide help (in the form of cytokines and/or cognate interactions) necessary for the expression of effector function by other cells in the immune system.

hemagglutinin: Any molecule which agglutinates erythrocytes.

hematopoiesis: The production of erythrocytes, leukocytes and platelets.

hematopoietic stem cells: Self-renewing stem cells that are capable of giving rise to all of the formed elements of the blood (i.e. leukocytes, erythrocytes and platelets).

heterozygous: Possessing different alleles at a given locus on the two homologous chromosomes.

homozygous: Possessing the same allele at a given locus on the two homologous chromosomes.

humanized antibody: A genetically engineered monoclonal antibody of non-human origin in which all but the antigen-binding CDR sequences have been replaced with sequences derived from human antibodies. This procedure is carried out to minimize the immunogenicity of therapeutic monoclonal antibodies.

humoral: Pertaining to extracellular fluid such as plasma and lymph. The term humoral immunity is used to denote antibody-mediated immune responses.

hybridoma: Hybrid cell line obtained by fusing a lymphoid tumor cell with a lymphocyte which then has both the immortality of the tumor cell and the effector function (e.g. monoclonal antibody secretion) of the lymphocyte.

hypervariable regions: Those amino acid sequences within the immunoglobulin and T-cell receptor variable regions which show the greatest variability and contribute most to the antigen or peptide–MHC binding site.

idiotope: An epitope made up of amino acids within the variable region of an antibody or T-cell receptor which reacts with an anti-idiotope.

idiotype: The complete set of idiotopes in the variable region of an antibody or T-cell receptor which react with an anti-idiotypic serum.

idiotype network: A regulatory network based on interactions of idiotypes and anti-idiotypes present on antibodies and T-cell receptors.

immune complex: Complex of antibody bound to antigen which may also contain complement components.

immunoadsorption: Method for removal of antibody or antigen by allowing it to bind to solid phase antigen or antibody.

immunofluorescence: Technique for detection of cell- or tissue-associated antigens by the use of a fluorescently tagged ligand (e.g. an anti-immunoglobulin conjugated to fluorescein isothiocyanate).

immunogen: Any substance which elicits an immune response. Whilst all immunogens are antigens, not all antigens are immunogens (see hapten).

immunoglobulin superfamily: Large family of proteins characterized by possession of ‘immunoglobulin-type’ domains of approximately 110 amino acids folded into two β-pleated sheets. Members include immunoglobulins, T-cell receptors and MHC molecules.

immunological synapse: A contact point between the T-cell and antigen-presenting cell which is generated by reorganization and clustering of cell surface molecules in lipid rafts. The synapse facilitates interactions between TCR and MHC and between adhesion molecules, thereby potentiating the TCR-mediated activation signal.

immunotoxin: A biochemical conjugate, or recombinant fusion protein, consisting of an immune targeting molecule such as an antibody or antibody fragment together with a cytotoxic molecule.

inflammasome: A multi-protein cytoplasmic complex that promotes inflammation by converting the IL-1β precursor into active IL-1β, and additionally by stimulating the generation of IL-18.

inflammation: The tissue response to trauma, characterized by increased blood flow and entry of leukocytes into the tissues, resulting in swelling, redness, elevated temperature and pain.

innate immunity: Immunity which is not intrinsically affected by prior contact with antigen, i.e. all aspects of immunity not directly mediated by lymphocytes.

interferons (IFN): IFNα and IFNβ (type I interferons) can be induced in most cell types, whereas IFNγ (type II interferon) is produced by T lymphocytes. All three types induce an anti-viral state in cells and IFNγ additionally acts in the regulation of immune responses.

interleukins (IL): Designation for some of the cytokines secreted by leukocytes.

internal image: An epitope on an anti-idiotype which binds in a way that structurally and functionally mimics the antigen.

invariant chain: A polypeptide which binds MHC class II molecules in the endoplasmic reticulum, directs them to the late endosomal compartment and prevents premature association with self peptides.

Ir (immune response) genes: The genes, including those within the MHC, that together determine the overall level of immune response to a given antigen.

ITAM: Immunoreceptor Tyrosine-based Activation Motifs are amino acid consensus sequences recognized by src-family tyrosine kinases. These motifs are found in the cytoplasmic domains of several signaling molecules including the signal transduction units of lymphocyte antigen receptors and of Fc receptors.

K (killer) cell:: A generic term for any leukocytes which mediates antibody-dependent cellular cytotoxicity (ADCC)

kinins: A family of polypeptides released during inflammatory responses and which increase vascular permeability and smooth muscle contraction.

KIRs: Killer cell Immunoglobulin-like Receptors found on NK cells, some gd and some ab T-cells. KIRs recognize MHC class I molecules and, like the C-type lectin receptors also found on these cells, can either inhibit or activate the killer cells. If ITIM sequences are present in their cytoplasmic domain they are inhibitory. KIRs lacking ITIMs can associate with ITAM-containing adaptor molecules, in which case they can activate the NK cell or T cell.

knockout: The use of homologous genetic recombination in embryonal stem cells to replace a functional gene with a defective copy of the gene. The animals that are produced by this technique can be bred to homozygosity, thus allowing the generation of a null phenotype for that gene product.

leukotrienes: Metabolic products of arachidonic acid which promote inflammatory processes (e.g. chemotaxis, increased vascular permeability) and are produced by a variety of cell types including mast cells, basophils and macrophages.

ligand: General term for a molecule recognized by a binding structure such as a receptor.

linkage disequilibrium: The occurrence of two alleles being inherited together at a greater frequency than that expected from the product of their individual frequencies.

lipid raft: Cholesterol- and glycosphingolipid-rich membrane subdomain in which molecules involved in cellular activation become concentrated.

macrophage: Large phagocytic cell, derived from the blood monocyte, which also functions as an antigen-presenting cell and can mediate ADCC.

mannose binding protein (mannose binding lectin): A member of the collectin family of calcium-dependent lectins, and an acute phase protein. It functions as a stimulator of the classical pathway of complement activation, and as an opsonin for phagocytosis by binding to mannose, a sugar residue usually found in an exposed form only on the surface of microorganisms.

marginal zone: The outer area of the splenic periarteriolar lymphoid sheath (PALS) which is rich in B cells, particularly those responding to thymus-independent antigens.

margination: Leukocyte adhesion to the endothelium of blood vessels in the early phase of an acute inflammatory reaction.

mast cell: A tissue cell with abundant granules which resembles the blood basophil. Both these cell types bear high affinity Fc receptors for IgE, which when crosslinked by IgE and antigen cause degranulation and the release of a number of mediators including histamine and leukotrienes.

medulla: Inner (central) region of an organ.

megakaryocyte: A bone marrow precursor of platelets.

membrane attack complex (MAC): Complex of complement components C5b –C9 which inserts as a pore into the membrane of target cells leading to cell lysis or apoptosis.

memory (immunological): A characteristic of the acquired immune response of lymphocytes whereby a second encounter with a given antigen produces a secondary immune response; faster, greater and longer lasting than the primary immune response.

memory cells: Clonally expanded T- and B-cells produced during a primary immune response and which are ‘primed’ to mediate a secondary immune response to the original antigen.

MHC (major histocompatibility complex): A genetic region encoding molecules involved in antigen presentation to T-cells. Class I MHC molecules are present on virtually all nucleated cells and are encoded mainly by the H-2K, D and L loci in mice and by HLA-A, B and C in man, whilst class II MHC molecules are expressed on antigen-presenting cells (primarily dendritic cells, macrophages and B-cells) and are encoded by H-2A and E in mice and HLA-DR, DQ and DP in man. Allelic differences are associated with the most intense graft rejection within a species.

MHC restriction: The necessity that T-cells recognize processed antigen only when presented by MHC molecules of the original haplotype associated with T-cell priming.

minor histocompatibility antigens: Non-MHC-encoded cell surface processed peptides which, in association with MHC-encoded molecules, contribute to graft rejection, albeit not usually as severe as that due to MHC mismatch.

naive lymphocyte: A mature T- or B-cell which has not yet been activated by encounter with antigen.

negative selection: Deletion by apoptosis in the thymus of T-cells which recognize self peptides presented by self MHC molecules, thus preventing the development of autoimmune T-cells. Negative selection of developing B-cells also occurs if they encounter high levels of self antigen in the bone marrow.

neutrophil: The major circulating phagocytic polymorphonuclear granulocyte. Enters tissues early in an inflammatory response and is also able to mediate antibody-dependent cellular cytotoxicity (ADCC).

NK (natural killer) cell: Large granular lymphocyte which does not rearrange nor express either immunoglobulin or T-cell receptor genes but is able to recognize and destroy certain tumor and virally infected cells in an MHC and antibody-independent manner.

NKT cell: NK1.1 + lymphoid cells with a morphology and granule content intermediate between T-cells and NK cells. They express low levels of aβ TCR with an invariant α chain and very restricted β chain specificity, recognize lipid and glycolipid antigens presented by the nonclassical MHC-like molecule CD1d, and are potent producers of IL-4 and IFNγ.

nude mouse: Mouse which is T-cell deficient due to a homozygous gene defect (nu/nu) resulting in the absence of a thymus (and also lack of body hair).

PAF (platelet activating factor): An alkyl phospholipid released by a variety of cell types including mast cells and basophils, which has immunoregulatory effects on lymphocytes and monocytes/macrophages as well as causing platelet aggregation and degranulation.

paracortex: The part of an organ (e.g. lymph node) which lies between the cortex and the medulla.

pathogen-associated molecular pattern (PAMP): Molecules such as lipopolysaccharide, peptidoglycan, lipoteichoic acids and mannans, which are widely expressed by microbial pathogens as repetitive motifs but are not present on host tissues. They are therefore utilized by the pattern recognition receptors (PRRs) of the immune system to distinguish pathogens from self antigens.

pattern recognition receptor (PRR): Receptors found on many different cell types in the immune system which enable them to recognize pathogen-associated molecular patterns (PAMPs). Amongst the large number of different PRRs are the mannose receptor (CD206), macrophage scavenger receptor (CD204) and the Toll-like receptors.

perforin: Molecule produced by cytotoxic T-cells and NK cells which, like complement component C9, polymerizes to form a pore in the membrane of the target cell leading to cell death.

periarteriolar lymphoid sheath (PALS): The lymphoid tissue which forms the white pulp of the spleen.

Peyer’s patches: Part of the gut associated lymphoid tissue (GALT) and found as distinct lymphoid nodules mainly in the small intestine.

PHA (phytohemagglutinin): A plant lectin which acts as a T-cell mitogen.

phage antibody library: A collection of cloned antibody variable region gene sequences which can be expressed as Fab or scFv fusion proteins with bacteriophage coat proteins. These can be displayed on the surface of the phages. The gene encoding a monoclonal recombinant antibody is enclosed in the phage particle and can be selected from the library by binding of the phage to specific antigen.

phagocyte: Cells, including monocytes/macrophages and neutrophils, which are specialized for the engulfment of cellular and particulate matter.

phagolysosome: Intracellular vacuole where killing and digestion of phagocytosed material occurs following the fusion of a phagosome with a lysosome.

phagosome: Intracellular vacuole produced following invagination of the cell membrane around phagocytosed material.

somatic hypermutation: The enhanced occurence of point mutations in the recombined immunoglobulin variable region V[D]J genes which occurs following antigenic stimulation and acts as a mechanism for increasing antibody diversity and affinity.

superantigen: An antigen which reacts with all the T-cells belonging to a particular T-cell receptor V region family, and which therefore stimulates (or deletes) a much larger number of cells than does conventional antigen.

surface plasmon resonance: A technique based upon changes in the angle of reflected light which occur upon ligand binding to an immobilized target molecule on a biosensor chip. This permits the observation of protein–protein interactions (such as antibody binding to an antigen) in ‘real-time’, i.e. by continuous monitoring of the association and dissociation of the reversible reaction.

TAP: The Transporters associated with Antigen Processing (TAP-1 and TAP-2) are molecules which carry antigenic peptides from the cytoplasm into the lumen of the endoplasmic reticulum for incorporation into MHC class I molecules.

T-cell receptor (TCR): The heterodimeric antigen receptor of the T lymphocyte exists in two alternative forms, consisting of α and β chains, or γ and δ chains. The αβ TCR recognizes peptide fragments of protein antigens presented by MHC molecules on cell surfaces. The function of the γδ TCR is less clearly defined but it can recognize native proteins on the cell surface.

T-dependent antigen: An antigen which requires helper T-cells in order to elicit an antibody response.

T-independent antigen: An antigen which is able to elicit an antibody response in the absence of T-cells.

thymocyte: Developing T-cell in the thymus.

titer: Measure of the relative ‘strength’ (a combination of amount and avidity) of an antibody or antiserum, usually given as the highest dilution which is still operationally detectable in, for example, an ELISA.

tolerance: Specific immunological unresponsiveness.

tolerogen: An antigen used to induce tolerance. Often depends more on the circumstances of administration (e.g. route and concentration) than on any inherent property of the molecule.

Toll-like receptors (TLRs): A family of pattern recognition receptors involved in the detection of structures associated with pathogens or damaged host tissues.

toxoid: Chemically or physically modified toxin that is no longer harmful but retains immunogenicity.

tumor necrosis factor (TNF, also called TNFα ): Together with the related cytokine lymphotoxin (TNFβ), was originally named for its cytotoxic effect on certain tumor cells, but also has important inflammatory and immunoregulatory functions.

variable (V) gene segments: Genes that rearrange together with D (diversity) and J (joining) gene segments in order to encode the variable region amino acid sequences of immunoglobulins and T-cell receptors.

vascular addressins: Cell adhesion molecules present on the luminal surface of blood and lymph vessel endothelium recognized by homing molecules which direct leukocytes to tissues with the appropriate ‛address’.